Endocrine System

Pathology
Dr. Sarah Alsawmhi
FRCpath, MD pathology, Oncopathology fellowship

Assistant professor, Faculty of medicine

Seiyun University
 Pituitary gland
• Pituitary adenoma

• Craniopharyngioma
 Pituitary adenoma
• The most common cause of hyperpituitarism is an anterior lobe
pituitary adenoma.
• Common in male(20-50yeras).
• Pituitary adenomas can be macroadenomas (greater than 1 cm in
diameter) or microadenomas.
• Functioning adenomas are associated with distinct endocrine signs and
symptoms, while nonfunctioning (silent) adenomas typically present
with mass effects, including visual disturbances.
• The two distinctive morphologic features of most adenomas are their
cellular monomorphism and absence of a reticulin network.
 Types of pituitary adenoma
Lactotroph adenomas Somatotroph adenomas Corticotroph adenomas

secrete prolactin and can secrete GH and present with secrete ACTH and present with
present with amenorrhea, gigantism in children and Cushing syndrome and
galactorrhea, loss of libido, and acromegaly in adults, impaired hyperpigmentation
infertility glucose tolerance, and diabetes
mellitus.
Normal pituitary gland
Pituitary adenoma
 Craniopharyngioma
Locally malignant(encapsulated).

Arise from remnants of Rathkei pouch.

Children and young adults.

Craniopharyngiomas average 3 to 4 cm in diameter.

 Variants of craniopharyngioma
Adamantinomatous craniopharyngioma Papillary craniopharyngioma

Most often observed in children Most often observed in adult

Contain palisading” of the squamous epithelium Contain both solid sheets and papillae lined by well-

(“wet keratin”) is a diagnostic feature of this tumor differentiated squamous epithelium.

Dystrophic calcification is a frequent finding. Lack the peripheral palisading

Additional features include cyst formation, fibrosis, Lack keratin, calcification, and cysts.

and chronic inflammation. Good prognosis

Poor prognosis
Adamantinomatous craniopharyngioma Papillary craniopharyngioma
 Thyroid gland
• Thyroiditis.

• Hyper and hypothyroidism

• Graves Disease

• Goiter

• Thyroid neoplasm.
 Thyroiditis

• Hashimoto thyroiditis.

• Riedel thyroiditis

• Granulomatous (de Quervain) thyroiditis

 1-Hashimoto thyroiditis
• Hashimoto thyroiditis is the most common cause of hypothyroidism in
regions where dietary iodine levels are sufficient.

• Symmetrical enlarged, firm with intact capsule and later decrease in size.

• Hashimoto thyroiditis is an autoimmune thyroiditis characterized by

progressive destruction of thyroid parenchyma, Hürthle cell change, and
mononuclear (lymphoplasmacytic) infiltrates, with germinal centers and
with or without extensive fibrosis.
Complications of Hashimoto thyroiditis

• Myxedema

• Lymphoma

• Papillary thyroid carcinoma

Hashimoto thyroiditis
Hashimoto thyroiditis
 2-Riedel thyroiditis
• Idiopathic
• Old age female
• Enlarged , hard and adherent and later decrease in size.
• Characterized by : dense fibrosis, atrophied follicles and chronic
inflammatory cells.
• Complications:
- Myxedema
- Pressure symptoms(Trachea- dyspnea)-(Esophagus-dysphagia)-
Recurrent laryngeal nerve- hoarseness of voice)
Riedel thyroiditis
3-Granulomatous /Subacute (de Quervain) thyroiditis

- Granulomatous (de Quervain) thyroiditis is a self-limited disease,

probably secondary to a viral infection(influenza, mumps and EBV).
- Enlarged, firm and painful .
- Presence of a granulomatous inflammation (giant cells,
macrophages, destruction of follicles and some fibrosis).
- Complications:
Mild myxedema and transient hyperthyroidism.
Granulomatous /Subacute (de Quervain)
thyroiditis
 Hyperthyroidism (Thyrotoxicosis)

It is hypermetabolic state caused by elevated circulating levels of free

T3 & T4.

Causes:
1-Thyrorid hyperplasia(Graves disease , 85% of cases)

2-Functiong adenoma.

3-Toxic nodular goiter .

 Hypothyroidism
It is inadequate thyroid hormone production.

Types:

1-Primary:

the most common cause is Hashimoto thyroiditis

2-Secondary:

caused by TSH deficiency

Cretinism in infancy or early child and Myxedema in older children and adults.
 Graves disease
Graves disease is the most common cause of endogenous
hyperthyroidism

Graves disease has a peak incidence between 20 and 40 years of age.

Women are affected as much as 10 times more frequently than men.
 Graves disease
The disease is characterized by a triad of clinical findings:
•Hyperthyroidism associated with diffuse enlargement of the gland

• Infiltrative ophthalmopathy with resultant exophthalmos

• Localized, infiltrative dermopathy, sometimes called pretibial

myxedema
 Pathogenesis of Graves disease
Graves disease is an autoimmune disorder characterized by the production
of autoantibodies against multiple thyroid proteins, most importantly the
TSH receptor.

• Thyroid- stimulating immunoglobulin(TSI): bind to the TSH receptor and

mimics the action of TSH, leading to T3&T4 release.

• Thyroid growth-stimulating immunoglobulin (TGI): directed against TSH

receptor, but these autoantibodies induce thyroid follicular proliferation.
 Graves disease
Gross:
• Mild and symmetrical enlarged thyroid glands

with smooth surfaces.

• Fleshy and red in color due to increased

vascularity
 Microscopic features of Graves disease
- Diffuse hypertrophy and hyperplasia of follicular epithelium(tall and
more crowded than usual, result in formation of small papillae but
without fibrovascular core.

- Colloid is decreased, pale and with scalloped margins.

- lymphoid infiltrates, consisting predominantly of T cells, along with

scattered B cells and mature plasma cells.

- Germinal centers are common.

Graves disease
 Goiter
• It is non-inflammatory, non-neoplastic enlargement of the thyroid gland

• Caused due to iodine deficiency, leading to compensatory increased

production of TSH, leading to hyperplasia of thyroid follicular cells and
enlargement of thyroid gland .
 Goiter
Goiter can be :

• Endemic: affects population in areas away from the sea like mountain,
due to deficiency of iodine in soil, water and food.

• Sporadic: affects female more than male, with peak incidence in young
adults with no clear causes.
 Goiter
• It passes in 3 phases:

1- Simple diffuse goiter:

First there is hyperplasia in response to increased TSH, and the follicles

are lined by crowded columnar cells, which form projections inside the
follicles

Gross: The thyroid gland is diffusely and symmetrically enlarged.

 Goiter
2-Colloid goiter:

If the demand for thyroid hormones decrease or iodine deficiency is

corrected , the follicular epithelium involutes.

The follicles contains abundant colloid and the lining follicular cells
are flattened.

Gross: the thyroid gland is diffusely and symmetrically enlarged

Cut surface is brown, glassy and translucent

 Goiter
3- Multinodular goiter:

With time, recurrent episodes of hyperplasia and involution produce

amore irregular enlargement of thyroid gland

Gross: Asymmetric enlargement of thyroid gland and can be massively

enlarged.
 Goiter
3- Multinodular goiter:

Cut section reveals variable sized nodules

containing variable amounts of brown gelatinous

colloid with areas of fibrosis, hemorrhage,

calcification and cystic changes

Microscopic features of Multinodular
goiter
• The gland appearance is variable with nodules formed of follicles
having flattened epithelium and filled with colloid alternating with
other nodules showing hyperplastic lining and little colloid .

• The nodules are separated by fibrous tissue

• Areas of calcification and hemorrhage are seen.

Microscopic features of Multinodular
goiter
 Thyroid neoplasm

• Thyroid adenoma

• Papillary carcinoma

• Follicular carcinoma

• Medullary carcinoma

• Anaplastic carcinoma
 1-Thyroid adenoma

• These are solitary masses of the thyroid tissue

composed of follicular epithelium and therefore

called as follicular adenoma.

• They are usually asymptomatic and

present as cold nodule on radio imaging scan.

 Thyroid adenoma
Thyroid adenoma

Morphologically:

- Solitary and having intact capsule.

- May see hemorrhage, calcifications and fibrosis.

- Cells often form uniform appearing follicles that contain colloid, but
they can have the following subtypes:
 Subtyping of follicular adenoma
• Macrofollicular.
• Microfollicular.
• Mixed microfollicular and macrofollicular
• Fetal.
• Hyalinized trabecular.
• Hürthle cell(oxyphilic, oncocytic) adenoma: Cells have eosinophilic,
granular cytoplasm.
• Clear cell follicular adenoma: cells have clear cytoplasm.
Follicular adenoma
Hyalinized trabecular type
 2-Papillary carcinoma

• It is the most common type of thyroid cancer

• Seen in 20-40 years old age group

• Spread by lymphatic rout

• Carries excellent prognosis

 Microscopic features of papillary CA:
• Papillae with fibrovascular core

• Calcifications (Psammoma bodies)

• Overlapping of the cells

• Cancer cells have diagnostic nuclear features:

Fine chromatin leading to ground glass or Orphan Annie eye nuclei

Intranuclear inclusions(Pseudoinclusions) or intranuclear longitudinal

grooves.
Papillary thyroid carcinoma
Papillary thyroid carcinoma
Papillary thyroid carcinoma
 3-Follicular carcinoma

• It is the second most common form of thyroid cancer

• Seen in women of older age (40-50 years)

• Vascular invasion is common

 Microscopic features of follicular CA:

• Presence of cells forming small follicles having colloid with

No psammoma bodies.

• Differentiation from follicular adenoma is based on the presence of

capsular and vascular invasion.
Capsular invasion of follicular
carcinoma
Vascular invasion of follicular carcinoma
 4-Medullary carcinoma

• Arise from parafollicular cells/C cells and secrete calcitonin.

• Associated with multiple endocrine neoplasia syndrome(MEN II).

• Associated with amyloidosis.

 Microscopic features of medullary CA:
• Polygonal, spindle cells in amyloid stroma.

• C- cell hyperplasia.
 5-Anaplastic carcinoma

• Undifferentiated thyroid cancer.

• Have the worst prognosis.

• Seen mostly in elderly female patient.

• Microscopic features: Highly anaplastic cells with giant and spindle

cells
Anaplastic carcinoma
 Parathyroid gland

Increase reabsorption of Ca from renal tubules.

Decrease reabsorption of Phosphate from renal tubules.

Increase absorption of Ca from intestine.

Increase bone resorption –Increase osteoclastic activity.

 Hyperparathyroidism

Primary Secondary

Hyperplasia Chronic renal failure

Adenoma(Chief, clear, oxyphilic) Metabolic syndrome

Carcinoma of chief cells Rickets

Osteomalacia
 Adrenal gland
• Pheochromocytoma: Tumor of adrenal medulla, which produce
catecholamines.
• Arise from chromaffin cells.
Rule of 10:
• 10% are bilateral.
• 10% are extra-adrenal.
• 10% are malignant.
• 10% occur in children.
• 10% are not associated with hypertension.
Microscopic features of pheochromocytoma:
• Nests of chief or chromaffin cells with sustentacular cells called
(Zellballen) with abundant cytoplasm which contains catecholamine
granules.

• The cells have salt and paper appearance.

• Chromogranin and synaptophysin are positive in chief cells.

• S-100 positive in sustentacular cells.

Pheochromocytoma
Multiple Endocrine Neoplasia (MEN) Syndromes
AD MEN1
[Menin] Pituitary adenoma or hyperplasia
MEN I
(Wermer syndrome) Parathyroid hyperplasia
Pancreatic endocrine neoplasm/islet cell tumor , duodenal
gastrin producing carcinoids [both are a cause of
hypergastrinemia/ Zollinger– Ellison syndrome]

MEN IIA AD RET Medullary thyroid carcinoma & C cell hyperplasia

(Sipple syndrome)
Parathyroid hyperplasia
Pheochromocytoma
AD RET Medullary thyroid carcinoma & C cell hyperplasia
MEN IIB
Pheochromocytoma
( Gorlin syndrome)
Marfanoid body habitus